Activation Strategies in Image-Guided Nanotherapeutic Delivery

Therapeutic nanomaterials serve as an important platform for drug delivery under image guidance. Despite significant growth and broad applications, their design specifics remain a subject of continued interest primarily due to multifunctional factors involved, ranging from nanomaterial properties, imaging modalities, and therapeutic agents to activation strategies. This review article summarizes key findings on their design characteristics with a particular interest in strategies developed for therapeutic activation (release). First, their activation can be controlled using either an endogenous factor including low pH and glutathione or an external stimulation by light, ultrasound, or electromagnetic field. The former is passively controlled from a spatiotemporal aspect compared to the latter, which is otherwise actively controlled through drug linker photolysis, nanomaterial disassembly, or gate opening. Second, light stimulation serves a most notable strategy due to its essential role in controlled drug release, photothermal activation (hyperthermia), and photodynamic production of reactive oxygen species (ROS). Third, some of those activation strategies that rely on ultrasound, photothermal, photoacoustic, magnetic field, or X-ray radiation are dually functional due to their role in imaging modalities. In summary, this review article presents recent advances and new insights that pertain to nanotherapeutic delivery systems. It also addresses their technical limitations associated with tissue penetration (light), spatial resolution (ultrasound, hyperthermia), and occurrence of cellular resistance (ROS).